The present invention relates to pharmaceutically useful 6-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-3,4-dihydro-2(1H)-quinolino ne with a novel crystalline form.
The U.S. Pat. No. 4,678,785 discloses that 5-3,4-dihydrocarbostyril-6-yl)-3,6-dihydro-1,3,4-thiadiazin-2-one [another nomenclature : 6-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-3,4-dihydro-2(1H)-quinolino ne, hereinafter referred to as compound(I)]which is useful as cardiotonics, is obtained by reacting 6-chloroacetyl-3,4-dihydro-2(1H)-quinolinone with ethoxythiocarbonylhydrazine in acetonitrile followed by recrystallizing the resulting crystals from a mixture of dimethylformamide and water. However, the thus obtained crystals (hereinafter referred to as .alpha.-form crystals of the compound (I)) are pale yellow cotton-like powders with low bulk density, tend to be electrified with static charge and are difficult to handle. The charged particles used to repel one another and easily diffuse into air. Furthermore., the .alpha.-form crystals of the compound (I) are unstable to be easily changed into different crystal form by the physical force. These properties are not satisfactory in precise measurability and workability during various handlings, especially in preparing pharmaceutical formulations.
The present inventors have made intensive investigations in order to solve the such problems and provide a novel crystal of the compound (I) which is suitable for preparing the pharmaceutical formulations. As a result, the inventors have found that the .alpha.-form crystals obtained by the method of aforesaid publication are heated, grinded or rubbed to give stable crystals of the compound (I) with good quality and convenience in handlings. These findings have resulted in the accomplishment of this invention.